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result(s) for
"Shafer, M. W."
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Integration of full divertor detachment with improved core confinement for tokamak fusion plasmas
2021
Divertor detachment offers a promising solution to the challenge of plasma-wall interactions for steady-state operation of fusion reactors. Here, we demonstrate the excellent compatibility of actively controlled full divertor detachment with a high-performance (
β
N
~ 3,
H
98
~ 1.5) core plasma, using high-β
p
(poloidal beta,
β
p
> 2) scenario characterized by a sustained core internal transport barrier (ITB) and a modest edge transport barrier (ETB) in DIII-D tokamak. The high-
β
p
high-confinement scenario facilitates divertor detachment which, in turn, promotes the development of an even stronger ITB at large radius with a weaker ETB. This self-organized synergy between ITB and ETB, leads to a net gain in energy confinement, in contrast to the net confinement loss caused by divertor detachment in standard H-modes. These results show the potential of integrating excellent core plasma performance with an efficient divertor solution, an essential step towards steady-state operation of reactor-grade plasmas.
Plasma fusion devices like tokamaks are important for energy generation but there are many challenges for their steady state operation. Here, the authors show that full divertor detachment is compatible with high-confinement high-poloidal-beta core plasmas and this prevents the damage to the divertor target plates and the first wall.
Journal Article
Taming harmful bursts and heat flux in high-confinement tokamak plasmas
2025
A major challenge in tokamak fusion research is first-wall erosion caused by steady heat loads and sudden energy bursts known as edge-localized modes. Divertor detachment reduces steady-state heat flux, while resonant magnetic perturbations can suppress these instabilities. However, integrating the two has been difficult because they require conflicting operating conditions. Here we demonstrate simultaneous achievement of resonant magnetic perturbations mitigated small edge-localized modes and impurity seeded partial divertor detachment in plasmas with an ITER-similar shape on the DIII-D tokamak. Experiments and simulations show that resonant magnetic perturbations facilitate detachment by redistributing particles, lowering the core density and increasing the scrape-off layer density, thereby reducing the amount of injected gas required. Cooling-gas injection eliminates the secondary heat-flux peak created by three-dimensional magnetic lobes, while edge cooling weakens the plasma response to the applied magnetic fields. These advances illustrate a viable pathway for integrating edge stability control with power exhaust in future fusion reactors.
Tokamak walls suffer erosion from steady and bursty heat loads. Here, the authors demonstrate that optimizing 3D magnetic field and cooling gas injection can tame destructive plasma bursts while enabling cooler, safer exhaust conditions.
Journal Article
Self-regulated oscillation of transport and topology of magnetic islands in toroidal plasmas
by
Austin, M. E.
,
Kobayashi, T.
,
Suzuki, Y.
in
639/766/1960/1136
,
639/766/34/866
,
70 PLASMA PHYSICS AND FUSION TECHNOLOGY
2015
The coupling between the transport and magnetic topology is an important issue because the structure of magnetic islands, embedded in a toroidal equilibrium field, depends on the nature of the transport at the edge of the islands. Measurements of modulated heat pulse propagation in the DIII-D tokamak have revealed the existence of self-regulated oscillations in the radial energy transport into magnetic islands that are indicative of bifurcations in the island structure and transport near the
q
= 2 surface. Large amplitude heat pulses are seen in one state followed by small amplitude pulses later in the discharge resulting in a repeating cycle of island states. These two states are interpreted as a bifurcation of magnetic island with high and low heat pulse accessibility. This report describes the discovery of a bifurcation in the coupled dynamics between the transport and topology of magnetic islands in tokamak plasmas.
Journal Article
Modulation of Neisseria gonorrhoeae Susceptibility to Vertebrate Antibacterial Peptides due to a Member of the Resistance/Nodulation/Division Efflux Pump Family
by
X.-D. Qu
,
Lehrer, R. I.
,
Shafer, W. M.
in
Amino Acid Sequence
,
Amino acids
,
Anti-Bacterial Agents - pharmacology
1998
We have previously described the antibacterial capacity of protegrin-1 (PG-1), a cysteine-rich, cationic peptide from porcine leukocytes, against Neisseria gonorrhoeae. We now report genetic and biochemical evidence that gonococcal susceptibility to the lethal action of PG-1 and other structurally unrelated antibacterial peptides, including a peptide (LL-37) that is expressed constitutively by human granulocytes and testis and inducibly by keratinocytes, is modulated by an energy-dependent efflux system termed mtr. These results indicate that such efflux systems may enable mucosal pathogens like gonococci to resist endogenous antimicrobial peptides that are thought to act during infection.
Journal Article
Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations
by
Kunz, Anjali N.
,
Bash, Margaret C.
,
Jerse, Ann E.
in
Animals
,
Anti-Bacterial Agents - pharmacology
,
Antibiotic resistance
2012
Background. Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA 91/95 and parC 86 mutations on gonococcal fitness. Methods. Mutant gyrA 91/95 and parC 86 alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR -79 mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection. Results. In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA 91/95 mutation conferred an in vivo fitness benefit to wild-type and mtrR -79 mutant gonococci. The gyrA 91/95 , parC 86 mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA 91/95 , parC 86 , mtrR -79 mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (Cip R ) mutant was selected during infection with the gyrA 91/95 , parC 86 , mtrR -79 mutant in which the mtrR -79 mutation was repaired and the gyrA 91 mutation was altered. This in vivo—selected mutant grew as well as the wild-type strain in vitro. Conclusions. gyrA 91/95 mutations may contribute to the spread of QRNG. Further acquisition of a parC 86 mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain Cip R .
Journal Article
Investigation of island formation due to RMPs in DIII-D plasmas with the SIESTA resistive MHD equilibrium code
by
Shafer, M. W.
,
Hirshman, S. P.
,
Canik, J. M.
in
70 PLASMA PHYSICS AND FUSION TECHNOLOGY
,
Axisymmetric
,
Deformation
2016
The SIESTA magnetohydrodynamic (MHD) equilibrium code has been used to compute a sequence of ideally stable equilibria resulting from numerical variation of the helical resonant magnetic perturbation (RMP) applied to an axisymmetric DIII-D plasma equilibrium. Increasing the perturbation strength at the dominant $m=2$, $n=-1$ resonant surface leads to lower MHD energies and increases in the equilibrium island widths at the $m=2$ (and sidebands) surfaces, in agreement with theoretical expectations. Island overlap at large perturbation strengths leads to stochastic magnetic fields which correlate well with the experimentally inferred field structure. The magnitude and spatial phase (around the dominant rational surfaces) of the resonant (shielding) component of the parallel current are shown to change qualitatively with the magnetic island topology.
Journal Article
Tailoring an Antibacterial Peptide of Human Lysosomal Cathepsin G to Enhance its Broad-Spectrum Action Against Antibiotic-Resistant Bacterial Pathogens
by
Willam Shafer
,
M. Hubalek
,
Samuel Katzif
in
Amino Acid Sequence
,
Amino Acid Substitution
,
Anti-Bacterial Agents - chemistry
2002
Neutrophils contain several cationic antimicrobial proteins or peptides (CAPs) that exert antibiotic-like action against bacteria. These host-derived antibiotics kill susceptible bacteria by oxygen-independent mechanisms. Considerable interest in their activity has been generated in recent years due not only to their likely important role in innate host defense against infection, but also their possible use as therapeutic agents in treating infections caused by antibiotic-resistant pathogens. We have studied the antibacterial properties of human lysosomal cathepsin G (cat G). This highly cationic serine protease contains at least three antibacterial regions that by themselves can exert antibacterial action against Gram-negative bacteria, such as Pseudomonas aeruginosa. Only one of these peptides, defined by residues 117-136 of full-length cat G, has bactericidal action against Gram-positive pathogens, such as Staphylococcus aureus. Due to the broad-spectrum antibacterial action of this peptide, we have sought to define the amino acids within its primary sequence required for this activity and have developed variants with improved activity. This review emphasizes the importance of both cationicity and hydrophobicity as necessary characteristics for the antibacterial action of CAPs. It also proposes the strategy that naturally occurring large human CAPs can be dissected to smaller CAPs and then modified to enhance their activity in vitro. This approach could prove beneficial to those interested in developing antimicrobial peptides as therapeutic agents.
Journal Article
Gonorrhea among Men Who Have Sex with Men: Outbreak Caused by a Single Genotype of Erythromycin‐Resistant Neisseria gonorrhoeae with a Single–Base Pair Deletion in the mtrR Promoter Region
by
Holmes, King K.
,
Xia, Minsheng
,
Whittington, William L. H.
in
Bacterial diseases
,
Bacterial diseases of the genital system
,
Bacterial Proteins
2000
During 1995-1997, an outbreak of 66 cases of gonorrhea caused by an erythromycin-resistant (Ery(r); MIC >/=1.0 microgram/mL) prototrophic (proto) auxotype IB-1 serovar of Neisseria gonorrhoeae occurred in King County, Washington; 65 cases involved men who have sex with men (MSM), which accounted for approximately 37% of infections among MSM during this period. Isolates from 19 of these 65 cases of infection were analyzed by DNA sequencing of the polymerase chain reaction-amplified promoter region of the mtrR gene and by pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA after NheI and SpeI digestion. Eighteen of the 19 isolates had a 1-bp A/T deletion in a 13-bp inverted repeat of the mtrR promoter region and shared a single PFGE type. Among MSM who provided data about sexual behavior, 37 (64%) of 58 MSM infected by the proto/IB-1 Ery(r) strain reported having >2 sex partners during the past 60 days, compared with 32 (30%) of 106 MSM infected by other strains (P<.001). This clonal outbreak of gonorrhea illustrates the ongoing need for behavioral preventive interventions among MSM.
Journal Article
Validating simulations of core tokamak turbulence: current status and future directions
2008
Validating predictive models of turbulent transport in magnetically confined plasmas requires comparisons of detailed fluctuation statistics, in addition to net energy flows. Using measurements from new and improved diagnostics on the DIII-D tokamak, we have performed a series of comparisons against predictions from the GYRO code. The development and application of synthetic diagnostics that model the spatial sensitivities of a given experimental fluctuation diagnostic is essential for these comparisons. At r/a = 0.56, we find very good agreement between the predicted and measured energy fluxes and fluctuation power spectra. At r/a = 0.8, however, the simulations underpredict the energy flows by a factor of seven and fluctuation amplitudes by a factor of 3 but successfully reproduce the shapes of the experimentally measured fluctuation power spectra. At both locations significant attenuation in the synthetic power spectra and fluctuation levels is observed relative to unfiltered levels. Additional results contrasting local and nonlocal simulation results and convergence in toroidal mode number spacing are presented.
Journal Article
Regulation of the MtrC-MtrD-MtrE Efflux-Pump System Modulates the In Vivo Fitness of Neisseria gonorrhoeae
by
Warner, Douglas M.
,
Folster, Jason P.
,
Shafer, William M.
in
Animals
,
Antibiotics
,
Antimicrobials
2007
The Neisseria gonorrhoeae MtrC-MtrD-MtrE multidrug-resistance efflux pump expels macrolide antibiotics, penicillin, and antimicrobial effectors of the innate defense. Mutation of the mtrR locus, which encodes a transcriptional repressor of the mtrCDE operon, increases gonococcal resistance to these agents. Here we report that, in a mouse infection model, an mtrR mutant is more fit than the wild-type bacteria. Consistent with derepression of the mtrCDE operon as the primary reason for the fitness benefit, an mtrR,mtrE double mutant and an mtrE mutant showed no difference in survival phenotype. Gonococcal mutants deficient in MtrA, an activator of the mtrCDE operon, exhibited significantly reduced fitness in vivo, and mtrA mutants with spontaneous compensatory mtrR mutations were selected during infection. These results confirm the importance of the MtrC-MtrDMtrE efflux-pump system during experimental gonococcal genital-tract infection and also illustrate an antibioticresistance mechanism that is accompanied by a fitness benefit rather than a fitness cost.
Journal Article